CA1330900C - Liquid nutritional formula for glucose intolerance - Google Patents

Abstract

LIQUID NUTRITIONAL FORMULA FOR GLUCOSE INTOLERANCE
ABSTRACT
An improved nutritionally complete formula containing a unique fiber-containing carbohydrate blend, at a relatively low concentration; a unique fat blend, at a relatively high concentration;
protein; carnitine, myoinositol, vitamins and minerals, including chromium. This formula is for the dietary management of patients with glucose intolerance.

Description

133~9~
FIELD OF THE INVENTION:
The invention relates to improved enteral nutritional formulas and more particularly to formulas which provîde protein, low carbohydrate, high fat, dietary fiber and micronutrients specific to the needs of glucose intolerant individuals.

BACXGROUND OF THE INVENTION
Primary treatment for glucose intolerance is strict adherence to a diet which minimizes , postprandial glucose response, and in many cases, use of medications (insulin or oral hypoglycemic agents). The~American~Diabetes Assoclation (ADA) :-currently recommends~ a diet in which protein accounts :~
for 12-2~% total calories (kcal), carbohydrate for ;~
50-60% kcal, and fat for the remaining kcal (about 30%)~ Diabetes_Care 2~250-253, 1979. The ADA also ;~
recommends consumption of complex carbohydrates:that ~ :~
are high in dietary fiber ~40 g/day for men, 25g/day for women), and consumptlon of fats that are low in .
choles~erol (~300mg/day)~and low in sàturated fatty acids (polyunsaturated fatty acids . saturated fatty acids or P:S ratlo = 1 or greater), Diabetes Outlook ~-21:1-8, 1986. ~ ~ ;
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~:~ .25 ~ Most currently available liquid enteral :
: formulas comply, for the most part, with the ADA
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recommendations. One such enteral formula sold by Fresenius Diatetik, Bad Homburg, West Germany under : ;~

-2- 133~9~0 the name Diabetiker-Flussignahrun~T,H contains 43% kcal as carbohydrate, 37~ as fat and 20~ kcal as protein.
Enteral formulas commonly used in patients with glucose intolerance in the United Sta~es include Compleat~ nutritional formula (Sandoz Nutrition, Minneapolis, i~innesota), which contains 16~ kcal as protein, 48% kcal as carbohydrate, 36~ kcal from fat, and dietary fiber from fruits and vegetables, Enrich~
nutritional formula (Ross Laboratories, Columbus, Ohio), which contains 14.5% kcal as protein, 55% kcal as carbohydrate, 30,5~ kcal as fat, and dietary fiber from soy polysaccharide and Osmolite@ nutritional `-~
formula (Ross Laboratories, Columbus, Ohio) which contains 14.0% kcal as protein, 54.6% kcal as carbohydrate and 31.4% kcal as fat. ;~
The primary problem in following the ADA
guidelines with liquid diets is that these formulas empty ra~idly from the stomach and are absorbed very erficiently in the upper segments or the small ~owel. Stevens et al, JPEN 3:32, 1979, have ~hown ;
that 66~ each of a 500 kcal feeding of Osmolite nutritional formula and two other enteral formula diets emptied from the stomach in one hour, and that 95% of each feeding empties in two hours. This is at least twice as fast as the emptying rate of an isocaloric solid food meal.
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~3~ 133~900 Because of the rapid emptying rate of liquid nutritional formulas, rapid absorption of their carbohydrate sources also occurs, which increases potential for hyperglycemia in patients with glucose 5 intolerance. Cashmere et al, Fed Proc 43:392, 1984, have shown that blood glucose response from a 500 :~ kcal feeding, each, o Compleat and Enrich --~ :
nutritional formulas peaks in only 30 minutes in ~
.:
healthy volunteers. This is as rapid as the ~':
lo absorption rate of free glucose. Additionally, a study conducted at the University of Chicago, by -~
Dreutzler et al, (unpublished), has shown that 5 day ~-:
consumption of Enrich nutritional formula as the sole .
source of nut~ition resulted in an elevated glucose ~ :
response curve in patients with Type II diabetes mellitus; following 5 day consumption of the diet, ;~
peak glucose response was 5% higher than baseline, ;:
and integrated area under the glucose response curve was almost 8% higher thsn baseline. Data from these 20 studies indicate that the current ADA dletary ..
guide}ines are inappropriate~for liquid nutritional-dlets. :
Several studies have shown that manipulation of certain dietary components may be beneflcial to .
glucose intolerant individuals. For example, fructose is known to be more sIowly absorbed than glucose and has been reported to lower postprandial blood glucose and insulin response. Koivistoinen et ~ .

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133~900 al, CarbohYdrate Sweeteners in Foods and Nutrition, Academic Press, London, 1980. Dietary fiber has been ~ ~
reported to lower postprandial glucose response in :
patients with diabetes~ Kay et al, Diabetoloqia 20:18-21, 1981. .~-One study has suggested adding myoinosltol ;
to the diet of diabetic patients in order to prevent decreases in tissue myoinositol which are common in patients having diabetes mellitus and result in ~
; ~ . .
deranged sodium potassium ATPase regulation which produces a functional derangement within nerves, -;
retina and glomerulus. Diabetic Outlook 21:2, 1986.
The amino acid carnitine has been reported to reduce :~-~
serum lipids, trlgiycerides, cholesterol and ratty acids in patients with diabetes mellitus~ Abdel-~ziz ~;~ et al, Nutr. RePorts International 29:1071~1079, 1984. Chromium Is~known to function as a component of an organic complex with nicotinic acid and amino ~
:~; ; acids to form glucose tolerance factor required to `;~.
20 maintain glucose homeostasis. Wallach, J. Amer. ~
Coll. Nutr. 4:107-120, 1985. ~ ~.

S ~ Y OF THE INVENTION:
~- The present invention is~an improved .25 nutritionally complete enteral ormula for the dietary management of~patients with hyperglycemia, such as those with diabetes mellitus or stress-induced hyperglycemia. Tho lmprcvod fcrmula is ;~

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-S- 13309~0 comprised of about 33% kcal as carbohydrate, about 50% kcal as fat, and about 17% kcal as protein, and further contains a unique carbohydrate blend (law DE
corn starch, fructose, and soy polysaccharide), and a unique fat blend (high oleic safflower oil and soy oil) which are also beneficial to the dietary management of patients having a glucose intolerance.
The formula meets 100% of the U.S. R.D.A. for vitamins and minerals in about 1400 kcal, and further ;-::
lO contains chromium, selenium, molybdenum, myoinositol ~:
and carnitine. The invention overcomes tne primary ;~ complication, severe hyperglycemia, associated with the use of previous enteral diets in patients with glucose intolerance. If uncorrected, hyperglycemia ~.
~: 15 can result in dehydration, coma and ultimately daath ` ~ ln these patients.

Detailed DescriPtion of the Invention ~:
The fat source for the diabetic formula may be any fat source or blend of fat sources wh~ch provides the desired levels of saturated (less than 10% kcal), polyunsaturated (up to 1;0% kcal), mono-unsaturated fatty acids and alpha linolenic acid (0.5 .: .
to l.0% kcal) including soy oil, olive oil, marine ~: 25 oil, high oleic sunflower`or safflower oil, or cottonseed oil. Preferably the fat source is 10-15%
.: .:. .
unhydrogenated soy oil and 8S-90% high oleic ..
safflower oil. The amount of fat in the product may . .
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range from 45-60% of the total calories of the ~;
formula. Preferably, the fat comprises approximately ~ .4 50% of ~he total calories of the formula. An ~:
emulsifier is used to aid the stabilization of the ;:.
high fat formula. The emulsifier may be any suitable fat emulsifier such as mono- and di- glycerides, egg .
lecithin or soy lecithin. The preferred emulsifier : is soy lecithin. :~.
The carbohydrate source of the formula may ~: 10 be fructose, xylitol, corn syrup or hydrolyzed :.
:~ cornstarch. Acceptable carbohydrate sources for the ..
~: :
~ present formula are 20-67% of total carbohydrate as :: ~
fructose or xylitol with the remainder of the carbohydrate having a dextrose equivalent D.~. from ~:; 15 about 5-25. The preferred carbohydrate source is 20-43% fructose and 35-60% corn syrup solids having a ~:~
: D.E. of 5-25. However, the percent of fructose and ~ corn syrup solids of total carbohydrate is not :~: critical so long as the percent carbohydrate of total 20 calories is low (i.e., 20-37%). ~ :~
~: Another component of the carbohydrate s~stem ;~
~: of the high fat, low carbohydrate diabetic formula is ~
dietary fiber which comprises 20-35% of the . ~.;
, carbohydrate, preferably at a level of approximately ~ 25 20% of the carbohydrate. Soy polysaccharide is the ;~ ~ ; preferred source. . -.
The amount of carbohydrate present in the ...
.~ formula may range from about 20-37% of the total ~ :~
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~7~ 133~00 calories of the formula. Preferably the carbohydrate comprises approximately 33% of the total calories of :
the formula.
~:~ Artlficial sweeteners could alsa be used in -~
:~ 5 the present formula to enhance the organoleptic ~.
quality of the formula. Examples of suitable artificial sweeteners include saccharine and r~
aspartame.
The protein source or formula may be any -~.
suitable source for a nutritional formula such as casein, whey or soy protein The preferred source for~the present formula is sodium caseinate and s:odium calcium caseinate. The protein source of the , , :
: formula may be provided in the range of about 8% to .~.
~;~ 15 about 25% of the total calories and is preferably provided as about 17~ of the total calories of the formula.
To minimize the effect of the soy .:
: polysaccharide on the viscosity of the high fat, low carbohydrate formula and to minimize Maillard :
:browning caused by the:fructose and hydrolyzed corn starch in the fo;rmula while maintaining stability of the protein, pH control~is used during the ..
preparation of~the formula. ... `
The formula contains chromium at levels . ..
: between 50 and 400 mcg per 1422 kcal, with a : preferred level of approximately 200 mcg per 1422 ` kcal. Suitable sources of chromlum include chromium -8- 133G9~0 yeast, chromium acetate and chromium chloride. The preferred source is chromium chloride.
The formula also contains myoinositol at levels of approximately 1200 mg/1422 kcal and L-carnitine at approximately 200mg~1422 kcal.
Table l contains the preferred ingredients :
by amount per liter of the formula.

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Per Liter (1000 K calories) 5 Inqredients Preferred Amount Water 834.75 grams Soy oil 5.28 grams -High oleic Safflower Oil 48.11 grams 10 Sodium Caseinate 30.17 grams Sodium Calcium Caseinate 16.24 grams Corn Syrup solids (D.E. 20)33.29 grams ~: Fructose 37.41 grams Soy Polysaccharide 21.10 grams : 15 Soy Lecithin 2.17 grams :~ Magnesium Chloride 2.05 grams ~ .
: Sodium citrate 2.01 grams ~: Tricalcium Phosphate (micronized) 1.54 grams : Potassium Chloride 1.24 grams ~ 20 Potassium Citrate 1.01 grams .
::: Ascorbic Acid 509.76 mgs Myo-Inositol 957.00 mgs :: Choline Chloride 584.90 mgs ~: : : Dipotassium Phosphate 453.17 mgs :
: 25 L-Carnitine 159.60 mgs : Trace Minerals 114.40 mgs : ~: Ferrous Sulfate Zinc SuIfate Cupric Sulfate 0 Manganous Sulfate Oil Soluble Vitamins 58.00 mgs ~ .
Alpha-Tocopherol Acetate vitamins A Palmitate .
: ~ Phylloquinone 3s Vitamin D3 ~: Water Soluble Vitamins 78.98 mgs Thiamine Chloride Hydrochloride Riboflavin ; Calcium:Pantothenate `:` 40 FltcinAcid Cyanocobalamin ~: Pyrodoxine Hydrochloride .:~.
;~: Chromium Chloride 828.60 mcgs :::
:: 45 Sodium Selenite 154 mcgs : .;~
~; : . Sodium Molybdate 534.4 mcgs : ~.
~ . ", The fo~llowing is an example processing : method for the nutritional formula of the invention~

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-lO- 13309~0 I~ Preblends .
;~ The following mixtures are blended ~:~
separately~
: ~ A. Protein Oil Blend In this preblend, 7.34 lb, of high oleic saf1Ower oil and 0.805 lb, ~.
,:
of soy oil are placed in~a mixing ~:
kettle and heated wh:ile agitating ~ to a temperature range of ;~ 10 130-160F with a preferred range of 140-150F. To the heated oils 149.9 grams of soybean lecithin emulsifier are added and agitated until dissolved. Next, . ~
: lS 3.8~qrams` of~oil soluble vitamins ~ ~ :
A, D3, E and Kl are added and agitated~thoroughly. A
temper~ature range of 130-150F : .`.
is maintained until the oil blend~
~ ~ is~used. ~It:~should be noted~that : : the oil blend should be used : -~
within 12 hours of the time it is -: made to pre~ent:rancidity of the ~: :
oil and loss of the oil soluble :: 25 ~ vitamins~' potency~

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;~ : : To this oil blend, 3~38 lb~ of sodium ~.`
~ caseinate is added with agitation~ ;This slurry must ~ ~ .

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' -11- 13309~0 be held for a minimum of ten minutes at 130-150F
with agitation to allow dissolution of the protein before proceeding.
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B. CarbohYdrate Mineral Solution In a mixing kettle 7.73 lb. of -~
filtered tap water are heated to a temperature of 135-175F with a preferred temperature range of 150-160F. The following minerals are added to the heated water and agitated until dissolved:

; Magnesium Chloride 6 H20 134.3 grams ..
Potassium Chloride 8.1 grams` ~:-Sodium Citrate 2 H20 131.9 grams ~ :~-Potassium Citrate H20 65.8 grams Minerals: ~ ~ 7.5 grams Ferrous Sulfate 7 H20 Zinc Sulfate 7 H20 Copper-Sulfate 5 H20 Manganese Sulfate H20 Tricalcium Phosphate, micronized 100.9 grams .--~ Chromium Chloride 6 H20 54.2 mgs.
Sodium Selenite ~ 10.5 mgs.
Sodium Molybdate 2 H20 36.7 mgs. ~ ~ :
Dipotassium Phosphate 29.7 grams After the minerals are dis~solved 5.47 lb. of 20 D.E. hydrolyzed cornstarch àre added~to the 30 mineral slurry under agitation. After the hydrolyzed ~ ;
cornstarch has dissol~ed, 5.45 lb. of fructose are ` added and dissolved. The pH of the slurry is then .~
adjusted to a range of 6.30 to 7.0 with a preferred ~ ;
range of 6.30 to 6.~55 using 1 Normal citric acid to decrease tie pH or 1 Normal potassium hydroxide to :~

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-12~ 3a9~0 increase the pH. This pH range is desirable as it minimizes the browning of the fructose and improves the aesthetic and organoleptic characteristics of the final product. The slurry is held at the preferred ~:~ s range of,130-145F under agitation until used.
C. Protein Fiber Slurry ` In a mixing kettle 59.62 lb. of filtered tap water is heated to , ~ ~
~ 130-170F with a preferred range o lo of 150-160 F to enhance protein solubility. The specifled amounts :~
of dry ingredients are dry blended ~;
by hand and slowly added to the heated water with agitatio Sodium Caseinate 1.19 lb.
Sodium Calcium Caseinate 2.46 lb.
~; ~ Soy Polysaccharide 3.19 lb.

This mix is maintained at the preferred :
temperature range of 150-160F while agitating or twenty minutes to allow hydration of~the caseinates --;;
and the soy polysaccharide. After twenty minutes of agitation, the pH of this mix is adjusted to 6.30 to 25 7.00 with a~preferred range of 6.30~-6.55. This range of 6.3-6.55 is desirable to minimize the viscosity of this slurry as well as that of the final product ~: : : . ., :
~ while avoiding denaturation and subsequent ~ ~
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~ insolubility of the protein which occurs at pHs below . .,:
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-13- 13309~

6~30. 45% potassium hydroxide is used to increase ti1e pH and lN citric acid is used to decrease the pH. Addition of either 4s% potassium hydroxide or 1 N citric acid must be done very slowly to avoid localized "burning" or denaturation of the protein.
This mix is maintained at the preferred temperature range of 150-160F under agitation until used.
This slurry must be used within two hours of its preparation to avoid microbial`growth.
~; 10 II. Blendinq The Carbohydrate Mineral slurry is added to the Protein Fiber slurry under constant agitation. The Protein Oil blend is immediately added while agitating. While maintaining a preferred temperature of 130-150F, the mixture is agitated for a minimum of ten minutes. After at least ten minutes of agitation, the pH of the ~:~
mixture is~adjusted to 6.30-7.0 with a -~
preferred range of 6.30-6.s5 using lN -citric acid to decrease the pH or lN
potassium hydroxide to increase the I :
pH. The pH of 6.30-6.55 is desirable to minimize the Maillard brown1ng reaction between the protein and the fructose and to minimize the viscosity of the mixture induced by the soy polysaccharide.

' -14 133~G~

: III. Homoqenization and Pasteurization Procedure ~he blended mix is heated to a temperature ranc3e of from 145-175F
~ 5 with a preferred range of from ;~ 155-165F throuqh a plate or coil heater, then pumped through a deaerator with a vacuum range of from 8 inches to 17 inches of mercury with a preferred ~: 10 . range of from lo inches to 15 inches of ;:
mercury. The blended mix is emulsified ; in a single stage homogenizer at a pounds per square inch ~PSIG) range of ~:: , - , ~
from:700-1200 PSIG with a preferred ~:
lS range of from 980-llO0 PSIG. The `~ blended mix is then homogenized in a ~-dual stage homogenizer at a first stage ~ -:
PSIG r:ange of from 3500-4200 PSIG with ~-~
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a preferred PSIG range of from o 3900-4200 PSIG and a second stage PSIG
: ranqe of from 250-700 PSIG with a preferred PSIG range of from 400-600 : :
` PSIG. The mix passes through a hold ~:
tube~with a 16 second hold time at a ~ 25 ~temperature range of from 165-190F
; ~ : with a preferred temperature range of ~` from 165-175F. This step consti~
~: tutes high temperature short time ~;

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13309~0 (HTST) pasteurization. The mix is pumped through a plate cooler to assure a product temperature range of frcm 34-48F with a preferred product temperature range of from 39-44F. ~-~-: From the cooler board, the mix is pumped into a refrigerated hold tank :::
capable of maintaining the preferred product temperature with constant :~
agitation., ,,, , : ' IV. Water Soluble Vitamin Solution In a mixing kettle three lbs. of : filtered tap water are maintained at a : temperature range of 40-90F with a ~ .
:. ~" ~ .:
preferred temperature:range of : 60-80F. The required amounts of the following ingredlents are added to the water with agita~.ion~

All~ remaining~Water;Soluble Vitamlns s.2~grams 20 AscorbiC Acid~ ~ 33.4 grams Choline:~Chloride ~38.3 grams L-Carnitine 10.4 grams :~
Myoinositolj ~ i ~; 62.6 grams ~:
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When a}l ingredients are~dlssolved the pH of 5`~the:v;itamin:solutlon is~ adjusted~to 5.5 to lO with a ::; preferred range of 6.0-7.0~uslng:IN:~citric acid to ~ :, decrease the pH or lN potassium~hydroxide to increase :the pH. After an acceptabIe pH;ia attained, all of : ;~
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- ~33~0 the vitamin solution is slowly added to the processed mix in the hold tank with constant agitation. It should be noted that the pH range of the vitamin :~;
solution is critical as a low pH will cause 5 denaturation of the protein in the product and a high -pH will facilitate browning in the product and may allow development of high viscosity.
V~ Flavor SYstem In a mixing kettle, 2,5 lbs. of filtered tap water are maintained at a temperature range of 40-9OF with a .
~ preferred temperature range of ;~ ~ 60-90F, 136 grams of vanilla flavor :
:
is added to the water and agitated to dissolve before slowly adding to the tank with agitation. Other suitable ~-~
flavors could be added to provide variety and to improve organoleptic acceptability. :
VI. Final Product Total Solids Adjustment 47 lbs. of filtered water are added to , the blended mix in the hold tank with a ~ :~
constant agitation in order to assure a total solids range from 17-23% with a .
preferred total solids range from about .
19-20%. .

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. -17-~ O O , ~: VII. Fillinq_and Sterilization Containers such as cans or glass -bottles are filled with the liquid ..
formula and sterilized according to FDA `
guidelines. While the high fat, low ~: carbohydrate formula is preferably provided in a Ready to-Feed form, it may also be concentrated by increasing .~:-the total solids or spray dried to ;.
.~.. powder form by procedures which are .. -~
well known to those skilled in the .~.
art. The concentrate or powder are then:reconstituted for feeding by adding water. . `~
The following examples~lndicate that proto-: types of the inventive nutritiona}~formula improves ~:
the postprandial glucose response of patients having ~ :.
type II; diabetes melli~tus, as reflected~by a decreased peak glucose response~and a::decreased : :
; 20 integr~ated~area under~the glucose response curve when : compared to that from liquid formula diets that comply with ADA guidellnes. ~.

Example I ~
Nine male and~three.female subjects, 36 to :`:: : ~ : ::
: 67 years old, with Type~I~I diab~etes mellitus were ~.:
studied to determine whether lowering the level of carbohydrate ln enteral formulas will improve ~: . , ~ ;
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-18- ~ 3 3 ~

post~randial serum glucose response, and to determine the effects of soy polysaccharide fiber on serum giucose response in formulas containing either low or moderate levels of carbohydrate. To accomplish these objec~ives, each subject was given 75 g glucose tolerance test solution and were randomly assigned to receive four meal tolerance tests: 1) 500 kcal Diet A
(28.1% kcal as carbohydrate, s5.2% Xcal as fat, 16.7~
Xcal as protein); 2)~an example of the formula of the invention which contains 500 kcal Diet A with soy polysaccharide (lOg); 3) 500 kcal Diet B (53.3% kcal :~
as carbohydrate, 30% kcal as fat, 16.7% kcal as protein), and 4) 500 kcal Diet B with soy polysaccharide (10 g). Each subject received all ~; 15 four products, with 3-7 day intervals between products. Six subjects were on oral hypoglycemic agents, but none were provided prior to the 75 g ~ .... .
glucose tolerance test solution. ~uring all other test periods, the six subjects on oral agents received their usual drug at the usual dose prlor to initiation of t~e meal tolerance~tests.
Both Diet A formulations resulted in a relatively flat postprandial glucose response curve.
~: - Peak glucose response was only~28 mg above fasting with the inventive formula (Diet A with fiber), and .
31 mg above fasting for Diet A. This was a significant improvement in glucose response compared to that from the Diet B products; peak gIucose j :

-19-- ~ 3 3 ~

response from Diet A with Fiber was 61% lower than ~:
that from Diet B with Fiber, and peak response from .
Diet A was 66% lower than that from Diet B
(P~0.0001). Integrated area under the glucose 5 response curve from the two Diet A formulations was ;:~
also lower than that from the two Diet B
formulations. Diet A with Fiber resulted in a total area under the glucose response curve that was 53%
less than that from Diet B with Fiber, and Diet A
resulted in an area under the curve that was 54~ less than that of Diet B (P~0.0001).
Lowering the level of carbohydrate in - ~:
;enteral formula diets also has a positive effect on .~;
insulin response. 'eak insulin response rom Diet A
15 with fiber was only 22.2 uU above fasting, and that .
from Diet A only 24.9 uU above fasting. This was 40%
~; lower than the insulin response for that from Diet B :
;~ with fiber, and 33% lower than that from Diet B .. ~:
(P~0.0005). There~were no differences in time to insulin peak among the four diets. However, Diet A
with fiber of the invention resuIted in a total area under the insulin response curve that was 37% lower . ~.
~;. than that of Diet B with fiber (P~0.0008).
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Example II ~ :
A screening study was conducted to evaluate ~ ;
the acute effects of low-carbohydrte, xylitol- ` ~-containing enteral formula diets on blood glucose and ` ' ';; ' 1330~0~ ~

insulin response in 4 male and 5 female subjects, ~-44-66 years old, with Type II diabetes mellitus.
Each subject was randomly assigned to receive a 70 g glucose tolerance test solution and five 500 Xcal servings of the following diets containing two caloric distributions: Diet 1 = 20% kcal as protein, 25% kcal as carbohydrate, 55% kcal as fat with xylitol as 45% of total carbohydrate; Diet 2 = 20%
kcal as protein, 40% Xcal as carbohydrate, 40~ kcal lo as fat with xylltol as 45% of total carbohydrate;
Diet 3 = Diet 1 with xylitol as 66.7% of total ~; carbohydrate; Diet 4 = Diet 2 with xylitol as 66,7%
of total carbohydrate; and Diet 5 = Ensure HN
nutritional formula from Ross Laboratories, Col-~mbus, Ohio served as the control diet. Each subject ` received all five diets and the 70 g glucose .~.
tolerance test solution, with a three-to-seven day interval between tests.
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Results indicated that the lower the level of ~arbohydrate, the flatter the postprandial glucose ~ , response curve regardless of the level of xylitol contained in the formulas. Thus, the level of carbohydrate has more of an`effect on postprandial ~ .
glucose response than the~type of carbohydrate. PeaX
25 glucose response was only 26 mgidL above fasting from ~;
the 25% carbohydrate/67% xyl`itol diet and 35 mg/dL
:` àbove fasting from the 25% carbohydrate/45% xylitol ;~ ~ diet, a significant improvement (P~0.02) compared to ~ ' ' : ' ~

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that from Ensure HN (peak response: 98 mg/dL above fasting). ~lthough peak glucose response from the diets containing 40% kcal as carbohydrate was also less than that from Ensure HN, results were not 5 statistically signficant. However, because of the .
magnitude of the difference (43%-46% less than that ' :
from Ensure HN) practitioners would likely consider the difference to be clinically significant.
Likewise it is possible that the results would have 10 reached statistical significance wlth a larger number ~i of subjects.
All four low-carbohydrate diets tended to result in a lower glucose response than Ensure HN at every time interval evaluated. As such, total area 15 under the glucose response curve from the four ;~
low-carbohydrate diets was lower (P~O.OOOl) than that from Ensure HN. Total area under the glucose response curve ranged from 46~ below that of Ensure HN (40% carbohydrate:45% xylitol) to 59% lower than :
that from Ensure HN (25% carbohydrate:45% xylitol~
There were no statistical differences in serum insulin response among diets:at any time interval evaluated. This may be attributed to .
.- insulin resistance, which is common in patients with i 25 Type II diabetes mellitus, particularly since ~
patients withheld their oral agents the morning of ~ ;
the glucose tolerance test.

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Examples I and II show that lowering the level of carbohydrate in enteral formulas helps improve postprandial glucose response in patie~ts ~;~
~ wi~h Type II diabetes mellitus.
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Claims (5)

1. A liquid nutritionally complete enteral formula for the dietary management of patients with glucose intolerance characterized in that:
a) 8-25% of total caloric value is obtained from protein;
b) 20-37% of total caloric value is obtained from a carbohydrate blend wherein said carbohydrate blend comprises corn starch, fructose and soy polysaccharide;
c) 45-60% of total caloric value is obtained from a fat blend and wherein less than 10% of total formula calories is derived from saturated fatty acids, up to 10% of total formula calories from polyunsaturated fatty acids and the balance of fat calories from monounsaturated fatty acids;
d) at least the minimum U.S. RDA for vitamins and minerals;
e) effective amounts of the ultratrace minerals chromium, selenium, and molybdenum; and f) effective amounts of carnitine, taurine and myoinositol.

2. The liquid nutritional according to claim 1 wherein the carbohydrate blend is 20-43% fructose, 20-35% soy polysaccharide and 35-60%
hydrolysed cornstarch.

3. The liquid nutritional according to claim 2 wherein the corn starch has a dextrose equivalent of about 20.

4. The liquid nutritional according to claim 2 wherein the amount of soy polysaccharide is about 25-30% of total carbohydrates.

5. The liquid nutritional according to claim 2 wherein protein is about 17%, carbohydrate is about 33% and fat is about 50%.